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Gefitinib (IRESSA) is an oral medication that acts as a small molecule inhibitor of EGFR. There have been two Phase II trials demonstrating 250 mg/day has activity in pretreated patients with advanced NSCLC, however a survival advantage has not been shown in the population as a whole. This study was conducted to determine the impact of gefitinib on survival as monotherapy in patients with advanced NSCLC previously treated with chemotherapy.

Toxicity was somewhat higher in the gefitinib arm for rash (37% versus 10%) and diarrhea (27% versus 9%) and primarily grade I and II

The incidence of interstitial lung disease was 1% and equal in both arms

Survival analysis by EGFR expression is inconclusive

Author's Conclusions

Gefitinib (IRESSA) was well tolerated in this group of pretreated advanced NSCLC patients

There was not a statistically significant improvement in survival with gefitinib

Analysis of a number of biomarkers is ongoing

Clinical/Scientific Implications

Taken as a whole, this trial is disappointing and does not show improvement in survival with gefitinib in this population. Unfortunately the biomarker analysis of EGFR was inconclusive. This may in part be due to the fact that tissue was not available for analysis in many of the patients, particularly the Asian and non-smoking patients. Some patients do respond to gefitinib therapy, however, thus far markers predicting response to gefitinib have been elusive. This is in contrast to erlotinib which has shown improved survival and has been tied to the expression of EGFR. Further analysis of the biomarkers from the ISEL study are eagerly awaited. Because the population as a whole does not show a survival advantage with gefitinib, this agent should be considered in Asian patients and never smokers but broad utilization is not warranted at this time. Further clinical trials to identify the specific patient populations that benefit from gefitinib are warranted.